The Metabolic Basis of the Septic Multiple Organ Failure Syndrome: Abnormal Energetic Fuel Control, Pathophysiologic Proteolysis and Futile Cycling of Hepatically Synthesized Substrates

Abstract

The evolution of the host response to severe injury into a compensated septic process and its later deterioration into the pattern of interorgan metabolic abnormalities characteristic of the multiple progressive or sequential organ failure syndrome (7) is an enigma whose code is only now beginning to be broken. This process begins with a subtle transformation from a successful adaptive response to trauma and posttraumatic invasion by bacterial organisms into a host destructive process in which the normal humoral and cellular defense mechanisms are misapplied to the destruction of the body’s capillary endothelial barrier (93). It ends with the initiation of an interorgan pattern of excessive catabolism and increasingly enhanced synthesis of body fuels which can no longer be adequately utilized. Together these are the characteristic features of the disease process which we know as the multiple organ failure syndrome (MOFS) (76). This review will attempt to conceptually integrate those aspects of this process which lead to this metabolic dysfunction and where possible to suggest some of the metabolic and physiologic loci where therapeutic modalities may be directed.